Sound exposure dynamically induces dopamine synthesis in cholinergic LOC efferents for feedback to auditory nerve fibers

Abstract

Lateral olivocochlear (LOC) efferent neurons modulate auditory nerve fiber (ANF) activity using a large repertoire of neurotransmitters, including dopamine (DA) and acetylcholine (ACh). Little is known about how individual neurotransmitter systems are differentially utilized in response to the ever-changing acoustic environment. Here we present quantitative evidence in rodents that the dopaminergic LOC input to ANFs is dynamically regulated according to the animal’s recent acoustic experience. Sound exposure upregulates tyrosine hydroxylase, an enzyme responsible for dopamine synthesis, in cholinergic LOC intrinsic neurons, suggesting that individual LOC neurons might at times co-release ACh and DA. We further demonstrate that dopamine down-regulates ANF firing rates by reducing both the hair cell release rate and the size of synaptic events. Collectively, our results suggest that LOC intrinsic neurons can undergo on-demand neurotransmitter re-specification to re-calibrate ANF activity, adjust the gain at hair cell/ANF synapses, and possibly to protect these synapses from noise damage.

Gradients in the biophysical properties of neonatal auditory neurons align with synaptic contact position and the intensity coding map of inner hair cells

“…Thus, whether spontaneous rate and threshold are defined exclusively by pre-synaptic mechanisms or further shaped by post-synaptic mechanisms remains an unresolved issue. Indeed, the presence of lateral olivocochlear efferents on the terminals of auditory neurons has long made the possibility of post-synaptic modulation of spiking activity highly likely ( Wu et al, 2020 ).…”

Distribution of Kv3 Subunits in Cochlear Afferent and Efferent Nerve Fibers Implies Distinct Role in Auditory Processing

“…MOC efferent fibers, by regulating electromotility of OHCs, modulate the sensitivity of ' cochlear amplifier' and prevent hair cell damage upon noise exposure [51][52][53]. Similarly, LOC efferent fibers, at least in part by modulating glutamate release from IHC, protect type 1 afferents from excitotoxic damage [24,54]. Not surprisingly, neurotransmitter release from cochlear efferent fiber axons are modulated by multiple mechanisms [55,56].…”

“…Type 2 afferent, on the other hand, receives synaptic inputs from multiple outer hair cells (OHCs) [21,22]. Efferent nerve fibers originated from the lateral olivary complex of the brainstem (LOC efferent) contact the most distal segment of the type 1 afferents and are thought to modulate the IHC-type 1 afferent synaptic transmission [23,24]. Another group of efferent nerve fiber contacting the OHCs are originated from the medial olivary complex (MOC efferent) and regulate the sensitivity of sound detection system [23].…”

Purkinje Cell-Specific Knockout of Tyrosine Hydroxylase Impairs Cognitive Behaviors

“…One possibility is that Th+ PCs confer additional plasticity not seen in Th PCs that is adaptive for different environmental or pathological stressors, or that ectopic Th expression is a compensatory response to homeostatic stress (or some systemic indicator that something is wrong), which the cerebellum then tries to help correct by boosting its Th protein level. For example, Th expression is increased in expression in response to sound exposure in lateral olivocochlear (LOC) efferent neurons, which appears to be an adaptive response to changes in auditory nerve firing to possibly protect hair cell synapses from noise damage (Wu et al, 2020 ). On the other hand, increases in Th expression may be associated with negative consequences as well: spinocerebellar ataxias are associated with increased Th expression in the substantia nigra, which may confer risk for psychotic symptoms in these patients (Turk et al, 2018 ).…”